Published data indicate that 2-5% of the U.S. population has Fetal Alcohol Spectrum Disorder (FASD) - a set of physical anomalies and neurodevelopmental deficits caused by prenatal alcohol exposure (May & Gossage, 2001). Despite the profound public health burden, there have been no clinical trials that have attempted to directly address the neurodevelopmental deficits that are so debilitating in FASD. Extensive pre- clinical work (Thomas et al. and others) has provided evidence that choline supplementation is effective in attenuating the neurodevelopmental deficits caused by prenatal alcohol exposure in animal models. Our group has taken the initial steps toward translating this work to humans with two randomized, double-blind, placebo- controlled trials. We first conducted a pilot study to ensure the feasibility, tolerability, and safety of choline supplementation in 20 children with FASD (Fuglestad et al, 2013). Next, we completed a study of 40 additional participants with the goals of establishing a target dosage for young children, testing efficacy in the domain of memory, and determining a developmental window for choline's effects (detailed in `preliminary studies'). Briefly, our pilot data revealed that: 1. Children wih FASD consume insufficient dietary choline on average; 2. Choline supplementation was safe, tolerable and feasible for 2-5 year olds; 3. Supplementation for 9 months increased children's explicit memory performance relative to placebo; 4. Significant memory improvement was seen in 2-3 year olds but not 4-5 year olds. For 2-3 year olds, memory improvement was 21 percentage points in the choline arm compared to 2 percentage points in the placebo arm; 5. A dose ranging from 10-19 mg/kg was associated with the largest improvement in memory; 6. A very common single- nucleotide polymorphism (SNP) (rs12325817), related to endogenous choline production, appears to moderate the efficacy of choline for children with FASD. These findings directly inform the next study. Aim 1 involves evaluating a 19 mg/kg dose in 60 children with FASD, ages 2 to 5. This dosing scheme will optimize the neurocognitive benefits and further enhance tolerability of the intervention. In addition to continuing the evaluation of memory benefits from choline, Aim 2 adds measures of attention and executive function as possible additional targets. The NIH Toolbox Flanker Inhibitory Control and Attention Test and the Executive Function Scale for Early Childhood (pilot-tested during our last study) have been added. Aim 3 adds a longitudinal component - it will evaluate 40 children in the period two years after treatment to determine the permanency of choline's effects. Lastly, Aim 4 will further examine the role of known SNPs in choline synthesis as moderators to the observed treatment effects. In summary, the proposed study will continue the translation of choline's application - from experimental pre-clinical work to an evidence-based intervention for neurodevelopmental deficits in children with FASD.